Reducing Red Blood Cell Transfusions in Lower-Risk Myelodysplastic Syndromes

Adults with lower-risk myelodysplastic syndromes (MDSs) often become red cell (RBC) transfusion-dependent, with only a minority having durable responses to erythropoiesis-stimulating agents (ESAs). Investigators now report the final analysis of the industry-sponsored, multinational, open-label, phase 3 COMMANDS trial comparing luspatercept to epoetin alfa in transfusion-dependent patients with very low, low, or intermediate risk MDS (as defined by the Revised International Prognostic Scoring System). Patients who had not received prior ESA treatment were randomized to subcutaneous luspatercept (1 mg/kg titrated up to 1.75 mg/kg, once every 3 weeks) or subcutaneous epoetin alfa (450 IU/kg titrated up to 1050 IU/kg once per week) for at least 24 weeks.

With a median follow-up of 17 months, the primary endpoint — independence from RBC transfusion for 12 or more weeks plus a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks — was achieved by 110/182 (60%) of the luspatercept group versus 63/181 (35%) of the epoetin alfa group (P<0.0001). Higher luspatercept responses were observed in patients with SF3B1 mutations, positive ring sideroblast MDS subtype, lower baseline transfusion requirements (<4 units per 8 weeks), and serum erythropoietin levels <200 U/L. Fatigue, dyspnea, and thromboembolic events were more frequent with luspatercept; 13% of luspatercept recipients discontinued therapy due to treatment-emergent adverse events, versus 9% with epoetin alfa. Rates of progression to high-risk MDS or acute myeloid leukemia were low and did not differ between study arms.